Process for the preparation of ring acylated aromatic compounds



Patented Feb. 7 195( PROCESS FOR THE PREPARATION OF RING ACYLATEDAROMATIC COMPOUNDS Robert Everett Foster, New Castle, Del., assignor toE. I. du Pont de Nemours & Company, Wilmington, Del., a corporation ofDelaware No Drawing; Application May 18, 1948,

. Serial N0. 27,820

invention relates to organic chemistry and more particularly to theacylation of compounds having an aromatic nucleus.

The ring acylation of aromatic compounds has hitherto been carried outwith the assistance of catalysts such as aluminum chloride, zincchloride, iodine, hydroiodic acid, silica alumina gel, etc. Thesecatalysts are uneconomical in that they are required in relatively highproportions to the aromatic compounds being acylated and some of them,notably aluminum chloride, are destructive to certain sensitivecompounds such as furan. Moreover, acylation reactions employing thesecatalysts are almost invariably accompanied by substantial amounts oftarry residues.

JThisinvention has as an object the provision of a process whereby theformation of tarry residues in acylation is decreased. A further objectis the provision of a catalyst useful in much smaller proportions thanhitherto employed. Another object is the provision of acatalystcatalytically useful with sensitive aromatics. Other objectswill appear hereinafter.

These objects are accomplished by the following. invention wherein theacylation of an arcmatic compound having hydrogen on nuclear car-. bonand having a bivalent chalcogen atom of atomic weight less than 33, i.e., of integral atomic number of 812, n being an integer not more thantwo, attached to two discrete carbons at least one 'of which is of thearomatic nucleus, is accom-.

plished by reacting the aromatic chalcogen compound in molar excess witha carboxylic acid anhydride in the presence of a catalytic amount ofperchloric acid and at a temperature of 25200 C.

The aromatic compounds acylated in the process of this invention have anaromatic nucleus having hydrogen on nuclear carbon and have at least onenuclear carbon bonded to bivalent chalcogen of atomic weight lessthan,33., the molecule of the aromatic apart from the bivalent chalcogenbeing hydrocarbon or halogenated hydrocarbon. The chalcogen atom isattached to but two atoms and these are carbon. The aromatics thusinclude;

(a) Heterocyclic aromatic, i. e., five-membered ring compounds, havinghydrogen on nuclear carbon and having the chalcogen as the one heteroatom and having the extranuclear valences of the nuclear carbons otherthan those satisfied by hydrogen satisfied by hydrocarbon and/orhalogen;

' (b) Carbocyclic aromatic, i. e., six-membered ring compounds havinghydrogen on nuclear carbon and having a bivalent chalcogen atom attachedto a carbon of the-ring, the remaining 8 Claims. (Cl. 260329) valence ofthe chalcogen being satisfied by a hydrocarbon radical of one to sixcarbons.

In a preferred embodiment of this invention two to six molal proportionsof a five-membered heterocyclic compound having from one to four nuclearhydrogens and containing as the hetero atom a divalent chalcogen ofatomic weight less than 33 is reacted at a temperature of -l50 C. with amolal amount of a saturated aliphatic monocarboxylic acid anhydride offrom four to fourteen carbon atoms in the presence of a catalytic amountof perchloric acid, preferably 0.02 to 0.5 mole per cent of theanhydride employed, and the acylated heterocyclic compound formed isisolated.

The following examples in which parts are by weight are illustrative ofthe invention.

Example I A mixture of 68 parts of furan, 51 parts of 95% aceticanhydride and 0.5 part of a 5% solution of perchloric acid in aceticacid was refluxed (at -40 C.) for a total of seven hours after which itwas allowed to stand at room temperature for approximately seventyhours. The acid was hell tralized with aqueous 5% sodium hydroxidesolution and the organic layer was washed with Water until neutral tolitmus and dried over anhydrous magnesium sulfate. Unreacted furan andacetic anhydride were recovered by distillation at at mosphericpressure. Z-acetylfuran (22.6 parts, B; P. -71 C./19 mm.) was thenobtained by distillation in vacuo. There was practically no I residue inthe still pot.

. Example II thiophene, B. P. 98.5 C./ 18 mm. 46

Example III To a mixture of parts of anisole and 51 parts aceticanhydride was added 0.3 part of a.

5% solution of perchloric acid in acetic acid.

The mixture after heating for four hours at C." was allowed to stand atroom temperature for about forty hours. After neutralization of the acidand removal of unchanged reactants by distillation, l parts (7.7% yield)of o-acetylanisale, 13. P. 100-110 C./6 mm. and 10.2 parts 3 (14.3%yield) of p-acetylanisole, B. P. 115-1l7 C./6 mm.; M. P. 35-37 0., wereobtained.

The importance of the chalcogen requirement in the acylatable aromaticcompounds of this invention, i. e., aromatic compounds which are capableof being ring acylated by the process of the invention, is illustratedby the fact that benzene (78 parts of thiophene-free), in contrast toanisole, was found not to react when. treated under similar conditionswith acetic anhydride (51 parts) in the presence of perchl'oric acid(0.03 mole per cent based on the acetic anhydride). When phenol, achalcogen-bearing aromatic compound, but not an ethe1'.,was:r e-- actedwith acetic anhydride in the presence of perchloric acid, the productwas almost exclusively phenyl acetate, i. e., ring acetylation took;

place if at all, to a very minor extent.

The aromatic compounds acylated in the: process of this invention arearomatic ethers with the ether linkage, oxyor thio either an annua larmember of the aromatic. nucleus or attached. toannular carbon thereof.Thesearomatic ethers have hydrogen on annular or nuclear carbon.

The invention is then generic toaromatic com,- pounds having hydrogen onnuclear, i. e., arcmatic carbon, haying a. bivalent chalcogen, atomattached by at least one or s valences to nu" clear carbon and. havingany remaining valence. attached to, a monovalent hydrocarbon; radical,

of one to six carbons, and having any remaining valence of they nucleussatisfied, by hydrocarbon and/or halogen including phenetole, phenylcinyl ether, phenyl hexyl; ether, diphenyl ether, phenyl cyclohexylether, naphthyl methyl ether, phenyl methyl sulfide, benzofuran,benzothiophene, and their hydrocarbon. and halogen substitutedderivatives, e. g., Z-methylfuran, 2,5- dimethylfuran, 2 methylphenylfuran, 2- methylthiophene, B-methylthiophene, 2,3- and3,5-dimethylthiophene, 2.-phenylthiophene, di-.- thienylmethane,2-bromofuran, 2 -chlor,othiophene, 2-bromothiophene. p-chloroanisole, p,brcmophenetole. p-chlorophenyl methyl sulfide, etc. Of these, thepreferreibecause of.a.vai1. ability and good reactivity, are monocyclicchalcogen-containing aromatic compounds, whichv have five to six annularatoms in, the aromatic ring, have hydrogen on annular carborn, haye,

attached to at least one annular carbon atom,.

a chalcogen, and are, apart from thechalcogen,

hydrocarbon. The most preferred class are1thosewherein the aromaticcompound has hydrogen.

on nuclear carbon, has a bivalent chalcogen of, atomic number 812, wheren is an integer not greater than two, bondeditoat least one carbon of.the nucleus, any valence of the chalcogfin not bonded to nuclear carbonbeing satisfiedby a monovalent hydrocarbon radical 0.1v one to six,carbons. and is, apart from bivalent chalcogen, hydrocarbon.

In the process of this. invention. carboxylic acid anhydrides. i. e.,compounds, haying the, characteristic grouping in general are-suitableas, acylating agents ineluding propionic, butyric, pentanoidhexanoic,

heptanoic, hexahydrobenzoic, benzoic, phthalic,

succinic, adipic, and inaleic acid anhydrides. and.

they can be substituted for the acetic anhy dride of the examples forthe production of thecorresponding acyl derivatives. Becauseoi theirsuitable reactivity and availability, it is preferred,

4 however, to employ saturated monocarboxylic anhydrides, (RCOMO, Rbeing a saturated hydrocarbon radical, aliphatic in character, 1. e.,anhydrides of alkanoic and cycloalkanoic acids, said anhydridescontaining from four to fourteen carbon atoms- In the process, of thisinvention the molal ratio of acylatable aromatic compound to carboxylicacid anhydride can vary from about 1:1 to 20:1. Preferably there shouldbe a molal excess. of the aromatic compound being acylated. The molalratio most preferred is within the range of, 2:1. to 6:1. since, ingeneral, with these ratios the ring acylation reaction proceeds mostadvantageously;

The perchloric acid catalyst should be emplayed, in an amount of atleast 0.005 mole per cent'based on the molal amount of the anhydrideused. In general, not more than one mole per cent of the catalyst will?be employed, the preferred. amountbeing, from 0.02 to- 0.5 mole percent.v

The temperature, at which. the. reactionis; car. ried' out canbe from.25-2009 0., the. particular temperature, depending on. the; sensitivityof. the. particular rea entsbeing. processed. However, a, temperatureof.25-150 C. ispreferred since the. reaction proceeds. suitably at this.range. The. time of. reaction canlikewise vary widely, from one. to asmuch as. 80 hours or more, dependingto. a large, extenton thetemperature. At the temperature within. the. preferred. range, two to;twenty hours reaction. time. is. usuallysufiicient. for. good results.

The. process of, this. invention; is therefore: suitable for thepreparation of acyl heterocyclicsand 3,5'-dimethylthiop hene, 2 acetyl-5.- ethylthiophene, 2'-acetylphenyl1 methyl sulfide, 4-acetylphenyl'methyl sulfide, 3.-br.omoe4-methoxypropiophenone; Z-pentanoyl'anisole,etc.

The acylated, products. of this. invention are. useful as intermediatesfor. pharmaceuticalsand dyestufis, and. as perfume ingredients. plantgrowth regulantsand insecticides.

The foregoing detailed description has. been givenfor. clearness of,understanding only. andno unnecessary limitations arev to be understoodtherefrom. The invention. is not limited tothe exact details shown anddescribed for obvious modifications will. occur. to those skilled. inthe ar.

What" is claimed, is

l. A process for the preparation of. acetylanisole wherein aceticanhydride is. reacted. with; from-one to twenty moles, per moleofjacetic anhydride, of'anisole at a temperature within. the.range,25-200 C. in the presence of. 0.02- to 0.5 mole percent; based onthe. anhydride, of. per: ch-loric: acid;

2: A process for'thepreparation of acetylfuran. wherein aceticanhydride. is reacted with. from. one to twenty moles. per mole of.acetic anhydride, of, furan at a temperaturewithin therange 257 .00? C,in thepresence of 0.02 to 0.5. mole perphene wherein acetic anhydride isreacted with from one to twenty moles, per mole of acetic anhydride, ofthiophene at a temperature within the range 25-200 C. in the presence of0.02 to 0.5 mole per cent, based on th anhydride, of perchloric acid.

4. A process for the preparation of acetyl derivatives of five-memberedaromatic heterocyclic compounds having as the hetero atom a bivalentchalcogen of atomic number 811, where n is an integer and not mor than2, having hydrogen on nuclear carbon and containing only the chalcogen,carbon, and hydrogen wherein acetic anhydride is reacted with from oneto twenty moles, per mole of anhydride, of said aromatic heterocycliccompound at a temperature within the range 25-200 C. in the presence of0.02 to 0.5 mole per cent, based on the anhydride, of perchloric acid.

5. A process for the preparation of ring acylated aromatic carbocycliccompounds wherein acetic anhydride is reacted with from one to twentymoles, per mole of anhydride, of an arcmatic carbocyclic compound havinghydrogen on nuclear carbon, having on nuclear carbon a substituent XRwherein X is a bivalent chalcogen of atomic number 811, n being aninteger not greater than 2, and R is a monovalent hydrocarbon radical ofone to six carbons, and containing only carbon, hydrogen and thechalcogen at a temperature within the range 25-200 C. in the presence of0.02 to 0.5 mole per cent, based on the anhydride, of perchloric acid.

6. A process for th preparation of ring acylated aromatic compoundswherein a carboxylic the one chalcogen, and carbon, preferably not morethan 12, at a temperature within the range 25-200 C. in the presence or"0.02 to 0.5 mol per cent, based on the anhydride, of perchloric acid.'7. A process for the preparation of ring acylated aromatic compoundswherein a carboxylic acid anhydride is reacted at a temperature withinthe range 25-150 C. and in the presence of 0.02 to 0.5 mole per cent,based on the anhydride, of perchloric acid with an aromatic compoundcontaining carbon, hydrogen and bivalent chalcogen of atomic number 8n,wherein n is an integer not greater than 2, having hydrogen on nuclearcarbon, having the chalcogen attached to two separate carbons at leastone of which is a nuclear carbon.

8. A process for th preparation of ring acylated aromatic compoundswherein a carboxylic acid anhydride is reacted at a temperature withinthe range 25-150 C. and in the presence of 0.02 to 0.5 mole per cent,based on the anhydride, of perchloric acid with an aromatic compoundhaving hydrogen on nuclear carbon, containing one bivalent chalcogen ofatomic number 811., where n is an integer not greater than 2, bonded byone valence to nuclear carbon and by the other valence to carbon, anyextranuclear valence not satisfied by hydrogen and the chalcogen beingsatisfied by hydrocarbon or halogen radicals.

ROBERT EVERETT FOSTER.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Name Date Hartough et a1 Dec. 23, 1947 OTHERREFERENCES Number

1. A PROCESS FOR THE PREPARATION OF ACETYLANISOLE WHEREIN ACETICANHYDRIDE IS REACTED WITH FROM ONE TO TWENTY-MOLES, PER MOLE OF ACETICANHYDRIDE, OF ANISOLE AT A TEMPERATURE WITHIN THE RANGE 25-200*C. IN THEPRESENCE OF 0.02 TO 0.5 MOLE PER CENT, BASED ON THE ANHYDRIDE, OFPERCHLORIC ACID.